Description of Research Expertise

RESEARCH SUMMARY
The research program is dedicated to delineating genetic influences on behavior, including behavioral disorders. The program includes both human studies and genetic investigations of animal models for behavioral disorders. One investigation has been a genetic association study of bipolar (manic-depressive) disorder. A bipolar susceptibility gene has been localized to the peri-centromeric region of chromosome 18, and efforts are devoted to examining regional candidate genes for mutations which explain the linkage statistics.

Genetic dissection of a murine model for opioid addiction has revealed that most of the genetic variance in voluntary morphine intake is attributable to a locus on proximal chromosome 10, where the mu opioid receptor gene maps. This suggests that naturally-occurring variation in the mu opioid receptor gene influences voluntary morphine intake. Currently, we are examining two inbred strains of mice for genetic differences in the regulation of the mu opioid receptor gene. In a human extension of this research, the mu opioid receptor gene sequence is being examined among individuals on methadone maintenance for variations which may convey risk for opioid dependence. In an extension of the study of the mu opioid receptor gene in addictions, we are investigating mu opioid receptor interacting proteins for the roles they may play in human opioid dependence and in murine models of this addiction. We are examining the pharmacogenetics of naltrexone response among alcoholics, determining whether a functional mis-sense SNP (A118G, N40D) in the mu opioid receptor gene predicts therapeutic response among alcoholics.

We have also studied genetics of nicotine dependence, establishing a role for the alpha 3 and alpha 5 nicotinic receptor subunit genes in risk for nicotine addiction. The biological significance of the associated SNPs is being investigated.

We are studying genetics of anorexia nervosa, using a whole genome association approach.